The magnitude of airway remodeling is not altered by distinct allergic inflammatory responses in BALB/c versus C57BL/6 mice but matrix composition differs. Issue 6 (19th March 2021)

• Record Type: Journal Article
• Authors: Parkinson, James E; Pearson, Stella; Rückerl, Dominik; Allen, Judith E; Sutherland, Tara E
• Is Part Of: Immunology and cell biology. Volume 99:Issue 6(2021)
• Page Start: 640
• Page End: 655
• Publication Date: 2021-03-19
• Subjects: airway remodeling -- allergic airway inflammation -- collagen -- extracellular matrix -- mouse strain differences -- type 17 cytokines -- type 2 cytokines; Immunology -- Periodicals; Cytology -- Periodicals; 616.079
• DOI: 10.1111/imcb.12448
• Languages: English
• ISSNs: 0818-9641

Abstract

Abstract: Allergic airway inflammation is heterogeneous with variability in immune phenotypes observed across asthmatic patients. Inflammation has been thought to directly contribute to airway remodeling in asthma, but clinical data suggest that neutralizing type 2 cytokines does not necessarily alter disease pathogenesis. Here, we utilized C57BL/6 and BALB/c mice to investigate the development of allergic airway inflammation and remodeling. Exposure to an allergen cocktail for up to 8 weeks led to type 2 and type 17 inflammation, characterized by airway eosinophilia and neutrophilia and increased expression of chitinase‐like proteins in both C57BL/6 and BALB/c mice. However, BALB/c mice developed much greater inflammatory responses than C57BL/6 mice, effects possibly explained by a failure to induce pathways that regulate and maintain T‐cell activation in C57BL/6 mice, as shown by whole lung RNA transcript analysis. Allergen administration resulted in a similar degree of airway remodeling between mouse strains but with differences in collagen subtype composition. Increased collagen III was observed around the airways of C57BL/6 but not BALB/c mice while allergen‐induced loss of basement membrane collagen IV was only observed in BALB/c mice. This study highlights a model of type 2/type 17 airway inflammation in mice whereby development of airway remodeling can occur in both BALB/c and C57BL/6 mice despite differences in immune response dynamics between strains. Importantly, compositional changes in the extracellular matrix between genetic strains of mice may help us better understand the relationships between lung function, remodeling and airway inflammation. Abstract : This study highlights a model of type 2 and type 17 airway inflammation in mice whereby development of airway remodeling can occur in both BALB/c and C57BL/6 mice despite differences in immune response dynamics between strains. However, intriguing differences in extracellular matrix composition occur between allergen‐treated BALB/c mice and C57BL/6 mice.